1. Field of the Invention
The present invention concerns a method for preparing water-dispersible core-shell quantum dots stabilised with a layer of hydrophilic surface ligands, wherein the core is made up of PbS nanocrystals, the shell of CdS layer and the surface ligands are dithiocarbamates obtained by reacting amino acids with carbon disulphide, while maintaining the photoluminescence, colloid and a method of preparing colloid.
2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 37 CFR 1.98
In recent years, the technique of fluorescence imaging in NIR range has developed into a method which enables in vitro/in vivo imaging of biological structures. Biological tissues are transparent to the greatest extent in the range of 700-900 nm (NIR-I range), however, recently it has been shown that when using quantum dots (QDs) for in vivo imaging a more preferred range, due to reduced scattering of photons, deeper penetration of tissues and a greatly improved signal to noise ratio, is the spectral range of 1,000 to 1,400 nm (NIR-II). PbS quantum dots belong to the group of fluorophores having the most promising properties as emitters in the range of NIR-II.
An important factor limiting the use of quantum dots, including PbS, in the biological sciences is the fact that the most effective methods of synthesis lead to obtaining the QDs with the surface stabilised with hydrophobic ligands. Such QDs are dispersible in non-polar organic solvents such as chloroform or toluene, but not in water. Therefore, for biological applications it is necessary to obtain a hydrophilic surface of the QDs while introducing reactive functional groups that then can be used to engage the QDs with various (bio)molecules to make them bio-functional.
In the current scientific literature there can be found only a few reports on modification of surface of lead chalcogenides, aimed at obtaining lasting solutions of colloidal QDs in polar media. The strategy commonly used to convert the hydrophobic nanoparticles into nanoparticles dispersible in water is replacing the original hydrophobic ligands on the surface of the NCs with hydrophilic ligands, such as 11-mercaptoundecanoid acid or polyethylene glycol (PEG) phosphate. Another strategy involves intercalation of the amphiphilic ligand to, for example, oleic acid present on the surface of the NCs.
Nanocrystal semiconductors (quantum dots) soluble in water, known from the Patent Document U.S. Pat. No. 6,251,303, are obtained by using hydrophilic groups attached to the surface of the quantum dot. Compounds acting as ligands are the so-called bi- and trichelating compounds, i.e. having two or three groups that bind to the surface of the quantum dot. A hydrophilic part of ligands may comprise groups such as carboxylic acids, carboxylates, sulfonates, hydroxides, alkoxides, ammonium salts, phosphates. The core of the nanocrystals can be made up of semiconductor materials such as PbS, ZnS, ZnSe, ZnTe, Cds, CdSe, CdTe, GaN, GaP, GaAs, GaSb, InP, InAs, InSb, AlS, AlP, AlAs, AlSb, PbSe, Ge, Si and mixtures thereof. The shell of the quantum dots can be CdS, ZnS, ZnSe, CdSe, GaN, and magnesium chalcogenides.
The Patent Document WO2014089743 describes the preparation of nanocrystalline quantum dots using cationic or anionic precursor. The method is based on precipitation and isolating precipitated quantum dots. The core can be made up of compounds such as PbS, CdS, CdSe, CdTe, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, A1N, A1P, AlAs, AlSb, GaN, GaP, GaAs, GaSb, GaSe, InN, InP, InAs, InSb, TIN, TIP, TIAs, TISb PbSe, PbTe or mixtures thereof. The shell can be made up of compounds such as: ZnxCd1-xS, MgxCd1-xS, CaxCd1-xS, SrxCd1-xS, BaxCd1-xS, HgxCd1-xS, ScxCd1-xS, AlxCd1-xS, GaxCd1-xS, InxCd1-xS, MnxCd1-xS, FexCd1-xS, NixCd1-xS, CuxCd1-xS, MoxCd1-xS, PdxCd1-xS, AgxCd1-xS, PtxCd1-xS, AuxCd1-xS, CdS, CdSe, CdTe, ZnS, ZnSe, ZnTe, MgS, MgSe, MgTe, HgS, HgSe, HgTe, PbS, PbSe, PbTe, AlN, A1P, AlAs, AlSb, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, TIN, TIP, TIAs, TISb or mixtures thereof.
The Patent Document WO2010043053 describes water-soluble photoluminescent quantum dots having surface-available carboxylic groups, amino groups, or both. Quantum dots are coated with hydrophilic ligands having single-domain antibodies. The CdSe/ZnS nanocrystals are also coated with the layers containing hydrophilic ligands such as lysine, arginine, proline, valine, alanine, glycine.
The Patent Document CN101805606 describes a method for preparing monodispersive quantum dots using silver dithiocarbamate as a precursor to obtain them. The final products are Ag2S quantum dots.
However, these methods do not allow to achieve fully satisfactory stability in biological buffers. What is worse, in all cases a significant decrease in the intensity of photoluminescence was observed.